OBJECTIVETo investigate the genetic association pattern between single-nucleotide polymorphisms (SNP) in the interleukin-1 receptor-associated kinase 4 (IRAK-4) gene and allergic rhinitis (AR).

METHODSA population of 379 patients with the diagnosis of AR and 333 healthy controls who lived in Beijing region was recruited. A total of 8 reprehensive marker SNP which were in IRAK-4 gene region were selected according to the Beijing people database from Hapmap website. The individual genotyping was performed by MassARRAY platform. SPSS 13.0 software was used for statistic analysis.

RESULTSSubgroup analysis for the presence of different allergen sensitivities displayed associations only in the house dust mite-allergic cohorts (rs3794262: P = 0.0034, OR = 1.7388; rs4251481: P = 0.0023, OR = 2.6593), but not in subjects who were allergic to pollens as well as mix allergens.

CONCLUSIONThe potential genetic contribution of the IRAK-4 gene to AR demonstrated an allergen-dependant association pattern in Chinese population.

Adolescent ; Adult ; Aged ; Allergens ; genetics ; immunology ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukin-1 Receptor-Associated Kinases ; genetics ; immunology ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Rhinitis, Allergic, Perennial ; genetics ; immunology ; Rhinitis, Allergic, Seasonal ; genetics ; immunology ; Young Adult

Orai1 is the key subunit of the Ca2+-release-activated Ca2+ channel. Our previous report has demonstrated that Orai1 expression in the airway was upregulated in the ovalbumin (OVA)-induced allergic rhinitis (AR) mouse models. To observe whether inhibition of Orai1 expression in the airway could suppress symptoms in a murine model of AR and to assess the impacts of this inhibition on the responses of local and systemic immunocytes, we administered recombinant lentivirus vectors that encoded shRNA against ORAI1 (lenti-ORAI1) into the nostrils of OVA-sensitized mice before the challenges, and analyzed its effect on allergic responses, as compared with the unsensitized mice and untreated AR mice. Administration of lenti-ORAI1 into the nasal cavity successfully infected cells in the epithelial layer of the nasal mucosa, and significantly decreased the frequencies of sneezing and nasal rubbing of the mice. Protein levels of leukotriene C4, OVA-specific IgE, and IL-4 in the nasal lavage fluid and serum and eosinophil cation protein in the serum were also significantly reduced by lenti-ORAI1, as were the mRNA levels of these factors in the nasal mucosa and spleen. These data suggested that administration of lenti-ORAI1 into the nasal cavity effectively decreased Orai1 expression in the nasal mucosa, alleviated AR symptoms, and partially inhibited the hyperresponsiveness of the local and systemic immune cells including T cells, B cells, mast cells and eosinophils that are involved in the pathogenesis of AR.
Animals ; Calcium Channels/analysis/*genetics/immunology ; *Down-Regulation ; Eosinophil Cationic Protein/blood/genetics ; Glutathione Transferase/blood/genetics/immunology ; Immunoglobulin E/blood/genetics/immunology ; Interleukin-4/blood/genetics/immunology ; Lentivirus/genetics ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa/immunology/metabolism ; Ovalbumin/immunology ; RNA, Messenger/genetics ; RNA, Small Interfering/*administration & dosage/genetics ; Rhinitis, Allergic, Perennial/*genetics/immunology ; Spleen/immunology/metabolism ; *Transfection

OBJECTIVETo study the preparation of recombinant house dust mite group 1 allergen vaccine (chitosan-pVAX1-Derp1 nanoparticles, pVAX1-Derp1/CS) and to investigate the efficacy and mechanism of intranasally given chitosan-pVAX1-Derp1 nanoparticles on mouse model with allergic rhinitis (AR).

METHODSThe chitosan-pVAX1-Derp1 nanoparticles was prepared by complex coacervation, and its nature was identified and analysed. A total of 40 BALB/c rats were randomly divided into 5 groups: the normal group (group A), the AR model group (group B), the chitosan (CS) prevention group (group C), the pVAX1-Derp1 prevention group (group D), and the pVAX1-Derp1/CS prevention group (group E). The nasal cavity of rats in the group B, C, D and E were dripped with phosphate buffered saline (20 µl), CS (20 µl), pVAX1-Der p1 (20 µl), pVAX1-Derp1/CS nanoparticles (20 µl) on the first day and day 8, once daily. Rats in the latter 4 group were sensitized with Der p1 and Al(OH)3 in day 15 and day 22, and challenged with Der p1 to establish AR model from day 36 to day 43, while rats in group A were treated with PBS. Then the level of cytokines in serum was assayed by ELISA, inflammatory reactions in nasal mucosa were analyzed by haematoxylin and eosin staining.

RESULTSpVAX1-Derp1/CS nanoparticles was successfully constructed, the mean grain size of pVAX1-Derp1/CS was (205.3 ± 12.8) nm, and the zeta potential was (30.5 ± 5.6) mV. In nasal mucosa tissue, group B and C showed significant allergic inflammation, while group D and E showed lighter allergic inflammation. Compared with the group B, the group D and E could effectively reduced serum IgE level and IL-4 level [group B: (120.0 ± 8.8) ng/ml, (248.7 ± 10.6) pg/ml; group D: (109.6 ± 14.5) ng/ml, (192.5 ± 10.2) pg/ml; group E: (88.1 ± 8.3) ng/ml, (165.7 ± 9.7) pg/ml; IgE: t value were 3.5, 6.9, all P < 0.01; IL-4: t value were 10.0, 15.2, all P < 0.01], and increased IFN-γ level [group B: (709.0 ± 26.5) pg/ml; group D: (856.3 ± 37.4) pg/ml; group E: (904.8 ± 37.7) pg/ml; t value were 8.2, 10.8, all P < 0.01)]. IL-10 level of group D [(129.9 ± 16.1) pg/ml] and E [(107.1 ± 11.8) pg/ml] was lower than IL-10 level of group B [(160.6 ± 24.2) pg/ml]. The difference were significantly (t value were 2.9, 5.5, all P < 0.05).

CONCLUSIONSChitosan can effectively encapsulate pVAX1-Derp 1 and inhibit nuclease degradation of the plasmid, the DNA vaccine has some preventive effect on AR animal model by nasal immunization.

Administration, Intranasal ; Animals ; Antigens, Dermatophagoides ; immunology ; Chitosan ; administration & dosage ; Cytokines ; blood ; Immunization ; methods ; Immunoglobulin E ; blood ; Mice ; Mice, Inbred BALB C ; Nanoparticles ; administration & dosage ; Nasal Mucosa ; immunology ; Plasmids ; Rhinitis, Allergic, Perennial ; prevention & control ; Vaccines, DNA ; genetics ; immunology